Abstract：
BACKGROUND: It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago.
METHODS: Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments.
RESULTS: The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 106 to 705 × 106 copies/mL plasma; P = 0.012), but MST was reduced compared to cats not given RetroMAD1™ (426 days vs 1006 days; P = 0.049). Cats treated with raltegravir and AZT had no significant changes in FeLV viral load over time, but p27 antigen load was decreased from T0 to T3-5 months in cats treated with raltegravir (median p27 antigen level reduced from 50.2% to 42.7%; P = 0.005). All other results were not significantly affected by the treatment provided. Importantly, statistically significant and substantial associations were found between age at FeLV diagnosis and survival time (P = 0.046, R2 = 18.6) and between FeLV viral load at T0 and survival time (P = 0.004, R2 = 44.4). Younger cats, and cats with higher levels of pretreatment FeLV RNA, had reduced survival times. Cats treated with RetroMAD1™ were typically younger (median age 2.0 vs 8.0 years), likely explaining the observed reduction in MST. A significant association was found between FeLV viral load and p27 antigen load at T0 (P = 0.015, R2 = 32.9).
CONCLUSIONS: Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.
METHODS: Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments.
RESULTS: The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 106 to 705 × 106 copies/mL plasma; P = 0.012), but MST was reduced compared to cats not given RetroMAD1™ (426 days vs 1006 days; P = 0.049). Cats treated with raltegravir and AZT had no significant changes in FeLV viral load over time, but p27 antigen load was decreased from T0 to T3-5 months in cats treated with raltegravir (median p27 antigen level reduced from 50.2% to 42.7%; P = 0.005). All other results were not significantly affected by the treatment provided. Importantly, statistically significant and substantial associations were found between age at FeLV diagnosis and survival time (P = 0.046, R2 = 18.6) and between FeLV viral load at T0 and survival time (P = 0.004, R2 = 44.4). Younger cats, and cats with higher levels of pretreatment FeLV RNA, had reduced survival times. Cats treated with RetroMAD1™ were typically younger (median age 2.0 vs 8.0 years), likely explaining the observed reduction in MST. A significant association was found between FeLV viral load and p27 antigen load at T0 (P = 0.015, R2 = 32.9).
CONCLUSIONS: Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.
摘要：
背景：对于猫白血病病毒（FeLV）感染提出的任何治疗方法是否有效，尽管该实体在60年前被描述过。
方法：在澳大利亚招募了18只进行性FeLV感染的宠物猫。在16只猫中试验了一种或多种抗病毒药物，而两只FeLV感染的猫不可处理，并作为未经处理的对照。六只猫只给药RetroMAD1™（0.5mg/kg，每天两次口服），一种市售的具有抗逆转录病毒活性的重组嵌合蛋白。三只猫只给药整合酶抑制剂raltegravir（10-15mg/kg，每天两次口服），一种用作高效抗逆转录病毒治疗人类免疫缺陷病毒（HIV-1）感染的药物。三只猫同时服用RetroMAD1™和raltegravir，和四只猫服用雷特格韦和逆转录酶抑制剂齐多夫定（AZT，5mg/kg，每天两次口服）。在治疗期间的两个时间点（T1-2个月和T3-5个月）测量FeLVRNA和p27抗原负荷，并与基线（治疗前）水平进行比较。使用线性模型评估对治疗的反应。还测定猫从FeLV治疗开始至死亡的中位存活时间(MST),并在治疗之间进行比较。
结果：接受抗病毒治疗的16只FeLV阳性猫的MST为634天，而两只未经治疗的对照猫从FeLV诊断到死亡的MST为780天。在用RetroMAD1™治疗的猫中，FeLV病毒载量从T0降低到T1-2个月（中位病毒载量从1339×106降低到705×106拷贝/mL血浆；P=0.012），但与未给予RetroMAD1™的猫相比，MST降低（426天vs1006天；P=0.049）。猫与raltegravir和AZT治疗的FeLV病毒载量随着时间的推移没有显著变化，但在接受雷替格韦治疗的猫中,p27抗原负荷从T0至T3-5个月降低(p27抗原水平中位数从50.2%降至42.7%;P=0.005).所有其他结果均未受到所提供的治疗的显著影响。重要的是,FeLV诊断年龄与生存时间(P=0.046,R2=18.6)以及T0时FeLV病毒载量与生存时间(P=0.004,R2=44.4)之间存在统计学上显著且实质性的关联.年轻的猫，和预处理FeLVRNA水平较高的猫，减少了生存时间。用RetroMAD1™治疗的猫通常较年轻（中位年龄2.0vs8.0岁），可能解释了观察到的MST减少。在T0时，FeLV病毒载量与p27抗原载量之间存在显着关联（P=0.015，R2=32.9）。
结论：这个小案例系列的结果没有为RetroMAD1™的使用提供令人信服的支持，raltegravir或AZT，单独或组合，用于治疗逐渐感染FeLV的猫。观察到的变化在生物学上微不足道。诊断时的年龄和FeLV病毒载量是有用的预后标志物，p27抗原浓度可用于预测病毒载量。更大的田间试验应该进行检查抗逆转录病毒疗法在FeLV阳性猫进行性感染，优选使用来自至少两类的三种或更多种药物，与人类抗逆转录病毒疗法一样。在FeLV感染率高于澳大利亚的国家，未来的研究将更容易。
方法：在澳大利亚招募了18只进行性FeLV感染的宠物猫。在16只猫中试验了一种或多种抗病毒药物，而两只FeLV感染的猫不可处理，并作为未经处理的对照。六只猫只给药RetroMAD1™（0.5mg/kg，每天两次口服），一种市售的具有抗逆转录病毒活性的重组嵌合蛋白。三只猫只给药整合酶抑制剂raltegravir（10-15mg/kg，每天两次口服），一种用作高效抗逆转录病毒治疗人类免疫缺陷病毒（HIV-1）感染的药物。三只猫同时服用RetroMAD1™和raltegravir，和四只猫服用雷特格韦和逆转录酶抑制剂齐多夫定（AZT，5mg/kg，每天两次口服）。在治疗期间的两个时间点（T1-2个月和T3-5个月）测量FeLVRNA和p27抗原负荷，并与基线（治疗前）水平进行比较。使用线性模型评估对治疗的反应。还测定猫从FeLV治疗开始至死亡的中位存活时间(MST),并在治疗之间进行比较。
结果：接受抗病毒治疗的16只FeLV阳性猫的MST为634天，而两只未经治疗的对照猫从FeLV诊断到死亡的MST为780天。在用RetroMAD1™治疗的猫中，FeLV病毒载量从T0降低到T1-2个月（中位病毒载量从1339×106降低到705×106拷贝/mL血浆；P=0.012），但与未给予RetroMAD1™的猫相比，MST降低（426天vs1006天；P=0.049）。猫与raltegravir和AZT治疗的FeLV病毒载量随着时间的推移没有显著变化，但在接受雷替格韦治疗的猫中,p27抗原负荷从T0至T3-5个月降低(p27抗原水平中位数从50.2%降至42.7%;P=0.005).所有其他结果均未受到所提供的治疗的显著影响。重要的是,FeLV诊断年龄与生存时间(P=0.046,R2=18.6)以及T0时FeLV病毒载量与生存时间(P=0.004,R2=44.4)之间存在统计学上显著且实质性的关联.年轻的猫，和预处理FeLVRNA水平较高的猫，减少了生存时间。用RetroMAD1™治疗的猫通常较年轻（中位年龄2.0vs8.0岁），可能解释了观察到的MST减少。在T0时，FeLV病毒载量与p27抗原载量之间存在显着关联（P=0.015，R2=32.9）。
结论：这个小案例系列的结果没有为RetroMAD1™的使用提供令人信服的支持，raltegravir或AZT，单独或组合，用于治疗逐渐感染FeLV的猫。观察到的变化在生物学上微不足道。诊断时的年龄和FeLV病毒载量是有用的预后标志物，p27抗原浓度可用于预测病毒载量。更大的田间试验应该进行检查抗逆转录病毒疗法在FeLV阳性猫进行性感染，优选使用来自至少两类的三种或更多种药物，与人类抗逆转录病毒疗法一样。在FeLV感染率高于澳大利亚的国家，未来的研究将更容易。
